In collaboration with cancer cell biologists at the Washington University School of Medicine and the University of Pennsylvania Abramson Cancer Center, as well as computational biophysicists at the University of Arizona, bioengineers and clinicians at Johns Hopkins University propose to create the Johns Hopkins Physical Sciences Oncology Center (PSOC). This PSOC will develop an integrated approach for a systematic, quantitative understanding of the forces mediating local invasion from the hypoxic primary tumor to distant organs, through single and collective invasion into the stromal matrix and confined migration along confining tracks, some of the early critical step in the metastatic cascade. To address the complexity of the combined effects of hypoxia, matrix microstructure and confinement on tumor cell invasion, we have developed three inter-related projects. Computational biophysicists will establish a computational core to systematically develop a quantitative understanding of forces in the metastatic cascade. PSOC projects will share innovative biophysical methods and experts. This PSOC takes a trans-disciplinary, integrated approach, combining the fields of physics, biomedical engineering, cancer biology, ecology, and clinical medicine, to transform our understanding of metastatic cancer, opening new paradigms for prognosis and treatment.